Tetrahydrobiopterin therapy for hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. When and how?

• Published in: Anales de pediatría (Barcelona, Spain : 2003) Spain : 2003), 2006-02, Vol.64 (2), p.146-152
• Main Authors: Baldellou Vázquez, A, Salazar García-Blanco, María I, Ruiz-Echarri Zalaya, María P, Campos Calleja, C, Ruiz Desviat, L, Ugarte Pérez, M
• Format: Article
• Language: Spanish
• Subjects: Adolescent; Biopterins - administration & dosage; Biopterins - analogs & derivatives; Biopterins - metabolism; Biopterins - therapeutic use; Child; Child, Preschool; Genotype; Humans; Infant; Infant, Newborn; Nitric Oxide Synthase - metabolism; Phenylalanine Hydroxylase - deficiency; Phenylalanine Hydroxylase - genetics; Phenylketonurias - drug therapy; Phenylketonurias - genetics; Phenylketonurias - metabolism
• ISSN: 1695-4033

Some patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency respond with a variable decrease in plasma phenylalanine levels after oral tetrahydrobiopterin (BH4) administration and are then able to tolerate higher dietary phenylalanine intake or even to discontinue a phenylalanine-restricted diet. BH4-sensitive patients are usually identified by means of a BH4 loading test, but consensus on the methodology of this test and the interpretation of its results is lacking. Consequently, a simple tool to identify which patients are likely candidates for this treatment and how they will progress in the long-term is required. A combined oral BH4 loading test with phenylalanine (100 mg/kg) and BH4 (20 mg/kg) was performed in 20 patients with hyperphenylalaninemia under dietary phenylalanine restriction. Independently of the genotype, the result was positive in all the 9 patients whose maximum phenylalanine level at diagnosis was below 815 nmol/ml. Currently, they are under treatment with tetrahydrobiopterin doses of 7-15 mg/kg/day. All these patients have been able to increase their oral phenylalanine intake. Six are currently following a normal diet and the remaining three are close to reaching this goal. None of the patients with a maximum phenylalanine level at diagnosis higher than 938 nmol/ml responded to the BH4 loading test. The maximum phenylalanine level at diagnosis seems to be a simple and reliable method to predict response to BH4 treatment. A high percentage of BH4-sensitive patients are able to discontinue a phenylalanine-restricted diet after long-term tetrahydrobiopterin treatment.